Development and deployment of a diverse mixture of economic and environmentally sustainable energy sources is important for international energy security. Nuclear power currently provides 20% of the US electricity, and a variety of fission and fusion energy concepts are under consideration for meeting future energy needs. After a brief review of current and proposed fission and fusion energy systems, some of the key fundamental materials science aspects associated with materials in these extreme operating environments will be summarized. A particularly daunting challenge is potential radiation-induced degradation of properties of structural materials associated with the intense high-energy neutron fluxes in fission and fusion reactors. The various microstructural changes associated with neutron irradiation and their consequences on material properties will be described. Irradiation can have a pronounced effect on the predominant deformation mechanisms in metals and alloys. Microstructural characterization of mechanically deformed materials is providing useful insight on deformation mechanisms, including the irradiation- and temperature-dependent transition between dislocation glide and diffusional creep regimes and reduction in ductility due to obstacle hardening and flow localization processes. The results of several experimental and computational modeling studies of dislocation interactions with radiation-induced defect clusters will be highlighted.